A greater number of cell and gene therapies are entering development, often with innovative modalities. One of the biggest challenges during CMC development is analytics. Analytics of biologics are complex enough, but with cell and gene therapies a new range of analytical issues arise. 

We interviewed Educo Life Sciences trainer Nadine Ritter to get her views on a career in cell and gene therapies. Nadine is an expert in CMC analytical for biologics vaccines, biosimilars and cell and gene therapies. Nadine provides some great advice for those moving into cell and gene therapies (from an analytical CMC perspective). She also discusses the biggest challenges within cell and gene therapies when it comes to analytics.

Watch the full interview below:

 

What would be your top three bits of advice for people moving into advanced therapies (from your analytical laboratory perspective)

It depends upon where you’re coming from, going into cell and gene is certainly a very exciting field and there is a lot of important therapies that are being developed, however, the CMC elements of it [cell & gene] are very challenging.

People starting from scratch

If you’re beginning your career and you are coming into this as a starting point in the industry, then one piece of advice would be to read everything we have done in the past. Read the guidance documents that have existed for the classic biologics, the current biologics and then also read what is being proposed for cell therapies and gene therapies. We tend to lump cell and gene together in one sentence, but they are in fact very different modalities and have very different processing and analytical issues associated with them.

There is a tremendous amount of information available at your fingertips if you know what you’re looking for and know where to look. When I first started my career there wasn’t any internet, so everything was learned by hunt and peck and word of mouth and going to meetings. But today if you have enough of a framework of knowledge to be able to place the pieces in context to each other and look at the chronological history then coming into this field new can be a very interesting way to get started.

Another piece of advice coming into this field new, do not underestimate coming into it at the lab level. I came in as a post doc back in the late 1980s and 90s and I learned that things that happened in QC are amazingly informative and educational and that the basic science knowledge you have gets you so far. Once you get into industry you must begin to understand the practicalities of it and the constraints of it. I have had numbers of people that have worked with me, that I’ve hired myself, gone on to incredibly rewarding careers because they came in through the QC lab level. At least at that point you cannot make any mistakes because they train you very well to do things very consistently, according to plan. It gives you some time and a good income to be able to find your foot in the field, and cell and gene therapy is right on the cutting edge of that.

“I learned that things that happened in QC are amazingly informative and educational”

 

People coming from small molecules

If you’re coming at it from a small molecule background, I would say do not be scared. It is a very different world. We have 250 years of experience with regulations and industry practises for chemical drugs and so there’s very well understood science, there’s very well understood regulations and very well understood compliance for small molecules. The same principles apply to biologically derived products and to cell and gene therapy products, but the practises are radically different so don’t be alarmed. Everything that you know about the principles will translate, although very little about the practises will. It can be very rewarding if you take that experience base and translate it into these modalities.

 

“The same principles apply to biologically derived products and to cell and gene therapy products, but the practises are radically different so don’t be alarmed.”

 

People coming from biologics/vaccines

Then the last population of people that are coming in from the biological side, from the existing well characterised biologic side or vaccines or plasma derivatives. Everything you learned so far will be magnified by what you are doing now. One of the fantastic movements I’ve seen in the cell and gene therapy CMC world is how many of my highly respected and experienced colleagues (who mad major contributions to biological/vaccine technologies and regulations) are now taking their seniority over to cell gene therapy products for CMC and that’s going to accelerate the remaining gaps. I think the cell therapy CMC space struggled a little bit because it was so novel and a lot of the people who were working in and developing it were either medical scientists or academic scientists and that gets you started of course but at some point, you need expertise that knows how to bring things into focus for a regulatory perspective and from a quality perspective. I am quite excited by the meetings I’ve been going to over the last couple of years to see how many of my colleagues that have done great work in the field, are going to make great strides in the other.

 

What are the biggest challenges in CGT from an analytical perspective?

The biggest challenge that we face is how to translate the principles and practises that we have learned with other modalities into these even more squishy modalities. I joke a lot about the fact we are dealing with squishy methods and squishy molecules and that is true, and with cell and gene therapy that is enhanced further.

The gene therapy world has a lot more consistency and control associated with their modality of product, they’re amenable to being stored as a drug substance and being formulated as a drug product and have longer shelf lives. However, with the cellular therapy products they are very challenging, and it does take the best science you can bring to the table to try to figure out how to do things correctly to achieve the compliance goals and achieve the control goals, the total control strategy for these modalities.

At the beginning of well characterised that is exactly what happened. There were no monoclonal antibodies that were being produced in a recombinant way in the beginning and very clever people got together and pulled science discussions together to have regulations generated, guidance’s generated, practises generated. As a result, the field exploded because smart people did their job and that is the same thing here. It does challenge you to try to wrap your head around how do I do this validation of that method, what are the principles that apply over here and how can I make that happen experimentally. That is a fascinating challenge, but we must do it. As patients we need the confidence of these products. We need to be confident that there are safe and effective and consistent and stable and so it’s not a challenge we can shirk off.

 

What are the most exciting areas in cell and gene?

I can give you a personal piece of information about the excitement of modalities and emerging therapeutics for things like cancer. I am getting to the age now where a lot of my friends and family members are having cancer. Fortunately, we have a lot of tools in the tool belt to help with those. If not cure them, certainly buy them a longer life, but I became very much acutely aware recently of the clinical impact of delays and timelines.

My younger brother was unfortunately diagnosed with aggressive cancer during COVID and although he was given 11 months to live, we got him to 22 and he died just two weeks before starting a clinical trial so I am aware of the need patients have. Every day that we delay means that it’s a day that somebody doesn’t get an opportunity to try the products, even in the clinical space. Do not waste time, don’t make mistakes that are avoidable if you only know what to do correctly. My biggest message to industry people who are wanting to move fast is; you know what must be done, when you need to do it, so do it right, do it once. Because if these patients really are the reason that motivates you to work on your products, then let’s make sure that we get it to them as quickly as possible.

But even as the FDA said during the COVID vaccine era we can’t cut quality corners because we’ll cause more risks than we’re benefiting people. We know what the rules are, and we know what to do so please don’t think that they don’t apply to you. Just do not make mistakes that cause you to reset the clock, just go forward with confidence that you know where you’re going and what you’re doing.

 

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